Minor sarcoplasmic reticulum membrane components that modulate excitation–contraction coupling in striated muscles

Abstract

In striated muscle, activation of contraction is initiated by membrane depolarisation caused by an action potential, which triggers the release of Ca 2+ stored in the sarcoplasmic reticulum by a process called excitation-contraction coupling. Excitation-contraction coupling occurs via a highly sophisticated supramolecular signalling complex at the junction between the sarcoplasmic reticulum and the transverse tubules. It is generally accepted that the core components of the excitation-contraction coupling machinery are the dihydropyridine receptors, ryanodine receptors and calsequestrin, which serve as voltage sensor, Ca 2+ release channel, and Ca 2+ storage protein, respectively. Nevertheless, a number of additional proteins have been shown to be essential both for the structural formation of the machinery involved in excitation-contraction coupling and for its fine tuning. In this review we discuss the functional role of minor sarcoplasmic reticulum protein components. The definition of their roles in excitation-contraction coupling is important in order to understand how mutations in genes involved in Ca 2+ signalling cause neuromuscular disorders.

Ca2+ handling abnormalities in early-onset muscle diseases: Novel concepts and perspectives

“…Aside the RyR1, the junctional sarcoplasmic reticulum is enriched in several other proteins including the structural proteins triadin and junctin, as well as minor constituents such as JP-45, junctate and humbug, mitsugumin-29, SRP-27/TRIC-A and junctophilin-1 [4,[27][28][29]. These minor constituents play a role in the fine regulation of Ca 2+ release from the SR or are involved in maintaining the structural integrity of the Ca 2+ release machinery.…”

“…SERCAs belong to class P-type ATPases and are responsible for replenishing the SR with Ca 2+ after its release following excitation-contraction coupling [2,4,5]. In striated muscle, SERCA activity can be modulated by two small regulatory proteins, sarcolipin and phospholamaban [5,6].…”

“…The transverse tubules (Ttubules) are invaginations of the plasma membrane and contain the voltage sensing dihydropyridine receptor (DHPR). The portion of the SR terminal cisternae membrane facing the T-tubules is called junctional face membrane and contains the ryanodine receptor Ca 2+ release channel (RyR1), regulatory and structural proteins such as JP-45, triadin and junctin as well as a number of other proteins that are part of the RyR1 Ca 2+ release channel macromolecular structure [1][2][3][4]. In skeletal muscle, the triad, i.e.…”

Depression of voltage-activated Ca2+release in skeletal muscle by activation of a voltage-sensing phosphatase

“…The process is rapidly and fully reversible so that upon membrane repolarization, muscle relaxation occurs driven by ATP-fuelled SR Ca 2+ uptake. Although the remarkable reliability of the DHPRRyR1 coupling keeps Ca 2+ release under the strict control of the membrane potential, there are possibilities for modulation of this process by several candidate molecules and accessory proteins (Dulhunty, 2006;Treves et al, 2009). For many of them, the physiological relevance of this modulation at the intact cell level remains unclear.…”

Trisk 32 regulates IP3 receptors in rat skeletal myoblasts

“…The binding of IP 3 to its receptor activates Ca 2+ release from the store to increase [Ca 2+ ] i [34]. RyRs have been shown to interact with a number of different proteins present in the triadic junction including, among others, calsequestrin, junctate, junctin, JP45, mitsugumins, and triadin (for review see [31]). From this group of SR membrane proteins triadin was first to be identified in rabbit skeletal muscle in 1990 [5,16] as a 95 kDa glycoprotein specifically located in the triads, and was later proved to decrease the extent of Ca 2+ release via RyRs [9,24].…”